It seems that Logitech Setpoint (comes with my MX5500 keyboard) eats all the media keys (play/pause, next, prev) and only passes them to apps it knows about. This is controlled with the C:\Program Files\Logitech\SetPointP\players.ini file. There are entries in there for lots of players, but not, of course, our favorite new player, plexamp. This is all documented fairly well in this post.

Unfortunately, I don't know what all the fields in that file mean and haven't been able to get a working entry in there. Anyone have any hints?

Here's the line I tried:
Plexamp=key,Plexamp.exe,xxx,xxx,xxx,xxx,xxx,xxx,xxx,xxx,0,1,Plexamp

Wow, great question, unfortunately I don 't have any advice. Have you tried asking their support what those fields mean? Maybe we could get it supported by default. Feel free to pass them my email elan at plex dot tv if they need contact info.

{btn|key|msg|emg|cmd|wac} = How to send the command to the program, key looks to be the favourite
exeName = executable filename, Plexamp.exe
wndClass = Window Class, so for an electron app this is likely, Chrome_WidgetWin_1 (Googling or using a window spy like Spy++ or the one that comes with AutoHotKey)
wndCaption = Window Caption/Title, it’s not visible, but it’s Plexamp
xxx = Probably some old option
play_delayplay = Key codes, a bit of Googling reveals that Chrome [1] likes these… &0xB3
pause = &0xB3
stop = &0xB2
prev = &0xB1
next = &0xB0
remove_flags = No idea
ShowOSD = Show the Logitech SetPoint OSD or not
menu_item = What to display in SetPoint